Brh2 Promotes a Template-Switching Reaction Enabling Recombinational Bypass of Lesions during DNA Synthesis

Nayef Mazloum, William K. Holloman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Accumulating evidence for Rad51-catalyzed DNA strand invasion during double-strand break repair features a 3′ single-stranded tail as the preferred substrate for reaction, but paradoxically, the preferred substrate in model reactions in vitro is the 5′ end. Here, we examined the Rad51-promoted 5′ end invasion reaction in the presence of Brh2, the BRCA2 family protein in Ustilago maydis. Using plasmid DNA and a homologous duplex oligonucleotide with 5′ protruding single-stranded tail as substrates, we found that Brh2 can stimulate Rad51 to promote the formation of a four-stranded complement-stabilized D loop. In this structure, the incoming recessed complementary strand of the oligonucleotide has switched partners and can now prime DNA synthesis using the recipient plasmid DNA as template, circumventing a lesion that blocks elongation when the 5′ protruding tail serves as template for fill-in synthesis. We propose that template switching promoted by Brh2 provides a mechanism for recombination-mediated bypass of lesions blocking synthesis during DNA replication.

Original languageEnglish
Pages (from-to)620-630
Number of pages11
JournalMolecular Cell
Volume36
Issue number4
DOIs
Publication statusPublished - 25 Nov 2009
Externally publishedYes

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Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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